Purpose: To compare gradient echo (GRE) and gradient echo sampling of spin echo (GESSE) sequences for the quantification of the oxygen extraction fraction (OEF) from combined quantitative BOLD and quantitative susceptibility mapping (QSM) with regard to accuracy, precision and parameter initialization. Methods: GRE and GESSE data were acquired from 7 healthy volunteers. QSM was applied to the GRE data and used as a regularization for the single-compartment quantitative BOLD fit to the GESSE and GRE data, respectively, to quantify OEF, deoxygenated blood volume (nu), R-2, and non-blood susceptibility (chi(nb)). Intersubject means within gray and white matter, respectively, were compared between GESSE and GRE (Student's t) and gray-white matter contrast was determined for each sequence separately. A single-and multi-compartment simulation was used to compare reconstruction accuracy. Results: Intersubject means and SDs for gray and white matter were OEF = 32.4 +/- 1.6%, nu = 2.9 +/- 0.1%, R-2 = 14.2 +/- 0.5 Hz, chi(nb) = -43 +/- 5 ppb for GESSE and OEF = 43.0 +/- 5.4%, nu = 3.5 +/- 0.4%, R-2 = 14.4 +/- 0.7 Hz, chi(nb) = -43 +/- 8 ppb for GRE with a significant difference (P < 0.05) for OEF and nu. Gray-white matter contrast was significant (P < 0.05) in all parameters for GESSE but only in nu and R-2 for GRE. All parameters reconstructed from GESSE had higher accuracy than from GRE in the single- but not multi-compartment simulation. Conclusion: GESSE yields higher parameter accuracy in simulated gray matter but produces unphysiological gray-white matter contrast in OEF in vivo. GRE produces uniform OEF maps in vivo and is more efficient, which could facilitate a clinical implementation, but revealed biases in simulation. The appropriate sequence should be chosen depending on application.